Isoprene-Derived Secondary Organic Aerosol Induces the Expression of MicroRNAs Associated with Inflammatory/Oxidative Stress Response in Lung Cells.

Exposure to fine particulate matter (PM2.5), of which secondary organic aerosol (SOA) is a major constituent, is linked to adverse health outcomes, including cardiovascular disease, lung cancer, and preterm birth. Atmospheric oxidation of isoprene, the most abundant nonmethane hydrocarbon emitted into Earth's atmosphere primarily from vegetation, contributes to SOA formation. Isoprene-derived SOA has previously been found to alter inflammatory/oxidative stress genes. MicroRNAs (miRNAs) are epigenetic regulators that serve as post-transcriptional modifiers and key mediators of gene expression. To assess whether isoprene-derived SOA alters miRNA expression, BEAS-2B lung cells were exposed to laboratory-generated isoprene-derived SOA constituents derived from the acid-driven multiphase chemistry of authentic methacrylic acid epoxide (MAE) or isomeric isoprene epoxydiols (IEPOX) with acidic sulfate aerosol particles. These IEPOX- and MAE-derived SOA constituents have been shown to be measured in large quantities within PM2.5 collected from isoprene-rich areas affected by acidic sulfate aerosol particles derived from human activities. A total of 29 miRNAs were identified as differentially expressed when exposed to IEPOX-derived SOA and 2 when exposed to MAE-derived SOA, a number of which are inflammatory/oxidative stress associated. These results suggest that miRNAs may modulate the inflammatory/oxidative stress response to SOA exposure, thereby advancing the understanding of airway cell epigenetic response to SOA.

Gene Expression Profiling in Human Lung Cells Exposed to Isoprene-Derived Secondary Organic Aerosol.

Secondary organic aerosol (SOA) derived from the photochemical oxidation of isoprene contributes a substantial mass fraction to atmospheric fine particulate matter (PM2.5). The formation of isoprene SOA is influenced largely by anthropogenic emissions through multiphase chemistry of its multigenerational oxidation products. Considering the abundance of isoprene SOA in the troposphere, understanding mechanisms of adverse health effects through inhalation exposure is critical to mitigating its potential impact on public health. In this study, we assessed the effects of isoprene SOA on gene expression in human airway epithelial cells (BEAS-2B) through an air-liquid interface exposure. Gene expression profiling of 84 oxidative stress and 249 inflammation-associated human genes was performed. Our results show that the expression levels of 29 genes were significantly altered upon isoprene SOA exposure under noncytotoxic conditions (p < 0.05), with the majority (22/29) of genes passing a false discovery rate threshold of 0.3. The most significantly affected genes belong to the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription factor network. The Nrf2 function is confirmed through a reporter cell line. Together with detailed characterization of SOA constituents, this study reveals the impact of isoprene SOA exposure on lung responses and highlights the importance of further understanding its potential health outcomes.

Epoxide as a precursor to secondary organic aerosol formation from isoprene photooxidation in the presence of nitrogen oxides.

Isoprene is a substantial contributor to the global secondary organic aerosol (SOA) burden, with implications for public health and the climate system. The mechanism by which isoprene-derived SOA is formed and the influence of environmental conditions, however, remain unclear. We present evidence from controlled smog chamber experiments and field measurements that in the presence of high levels of nitrogen oxides (NO(x) = NO + NO2) typical of urban atmospheres, 2-methyloxirane-2-carboxylic acid (methacrylic acid epoxide, MAE) is a precursor to known isoprene-derived SOA tracers, and ultimately to SOA. We propose that MAE arises from decomposition of the OH adduct of methacryloylperoxynitrate (MPAN). This hypothesis is supported by the similarity of SOA constituents derived from MAE to those from photooxidation of isoprene, methacrolein, and MPAN under high-NOx conditions. Strong support is further derived from computational chemistry calculations and Community Multiscale Air Quality model simulations, yielding predictions consistent with field observations. Field measurements taken in Chapel Hill, North Carolina, considered along with the modeling results indicate the atmospheric significance and relevance of MAE chemistry across the United States, especially in urban areas heavily impacted by isoprene emissions. Identification of MAE implies a major role of atmospheric epoxides in forming SOA from isoprene photooxidation. Updating current atmospheric modeling frameworks with MAE chemistry could improve the way that SOA has been attributed to isoprene based on ambient tracer measurements, and lead to SOA parameterizations that better capture the dependency of yield on NO(x).

The effects of α-pinene versus toluene-derived secondary organic aerosol exposure on the expression of markers associated with vascular disease.

To investigate the toxicological effects of biogenic- versus anthropogenic-source secondary organic aerosol (SOA) on the cardiovascular system, the Secondary Particulate Health Effects Research program irradiation chamber was used to expose atherosclerotic apolipoprotein E null (Apo E-/-) mice to SOA from the oxidation of either α-pinene or toluene for 7 days. SOA atmospheres were produced to yield 250-300 µg/m(3) of particulate matter and ratios of 10:1:1 α-pinene:nitrogen oxide (NOx):ammonia (NH3); 10:1:1:1 α-pinene:NOx:NH3:sulfur dioxide (SO2) or 10:1:1 toluene:NOx:NH3; and 10:1:1:1 toluene:NOx:NH3:SO2. Resulting effects on the cardiovascular system were assessed by measurement of vascular lipid peroxidation (thiobarbituric acid reactive substance (TBARS)), as well as quantification of heme-oxygenase (HO)-1, endothelin (ET)-1, and matrix metalloproteinase (MMP)-9 mRNA expression for comparison to previous program exposure results. Consistent with similar previous studies, vascular TBARS were not increased significantly with any acute SOA exposure. However, vascular HO-1, MMP-9, and ET-1 observed in Apo E-/- mice exposed to α-pinene + NOx + NH3 + SO2 increased statistically, while α-pinene + NOx + NH3 exposure to either toluene + NOx + NH3 or toluene +NOx + NH3 + SO2 resulted in a decreased expression of these vascular factors. Such findings suggest that the specific chemistry created by the presence or absence of acidic components may be important in SOA-mediated toxicity in the cardiovascular system and/or progression of cardiovascular disease.

Effects of water chemistry and flow rate on arsenate removal by adsorption to an iron oxide-based sorbent.

Arsenate removal from water using an iron oxide-based sorbent was investigated to determine the optimal operating conditions and the influence of water composition on treatment efficiency. The novel sorbent with a high surface area was studied in flow-through column experiments conducted at different flow rates to quantify the effect of empty bed contact time (EBCT) on treatment performance. Arsenic removal efficiency declined with decreasing EBCT. Arsenic breakthrough curves at different EBCT values were successfully simulated with a pore and surface diffusion model (PSDM). Surface diffusion was the dominant intraparticle mass transfer process. The effect of water composition on arsenic removal efficiency was evaluated by conducting experiments with ultrapure water, ultrapure water with either phosphate or silica, and a synthetic groundwater that contained both phosphate and silica. Silica was more inhibitory than phosphate, and the silica in synthetic groundwater controlled the arsenic removal efficiency.

Effect of secondary organic aerosol from isoprene-derived hydroxyhydroperoxides on the expression of oxidative stress response genes in human bronchial epithelial cells.

Isoprene-derived secondary organic aerosol (SOA), which comprise a large portion of atmospheric fine particulate matter (PM2.5), can be formed through various gaseous precursors, including isoprene epoxydiols (IEPOX), methacrylic acid epoxide (MAE), and isoprene hydroxyhydroperoxides (ISOPOOH). The composition of the isoprene-derived SOA affects its reactive oxygen species (ROS) generation potential and its ability to alter oxidative stress-related gene expression. In this study we assess effects of isoprene SOA derived solely from ISOPOOH oxidation on human bronchial epithelial cells by measuring the gene expression changes in 84 oxidative stress-related genes. In addition, the thiol reactivity of ISOPOOH-derived SOA was measured through the dithiothreitol (DTT) assay. Our findings show that ISOPOOH-derived SOA alter more oxidative-stress related genes than IEPOX-derived SOA but not as many as MAE-derived SOA on a mass basis exposure. More importantly, we found that the different types of SOA derived from the various gaseous precursors (MAE, IEPOX, and ISOPOOH) have unique contributions to changes in oxidative stress-related genes that do not total all gene expression changes seen in exposures to atmospherically relevant compositions of total isoprene-derived SOA mixtures. This study suggests that amongst the different types of known isoprene-derived SOA, MAE-derived SOA are the most potent inducer of oxidative stress-related gene changes but highlights the importance of considering isoprene-derived SOA as a total mixture for pollution controls and exposure studies.